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snATAC-seq data cell composition analysis in Figure 1

Principal component analysis of cell type-specific pseudo-bulk ATAC profile (S Figure 2)

Beta cell

Alpha cell

Beta cell differential cCREs (pseudo-bulk analysis) in Figure 1

Differential cCREs (FDR<0.1) between T2D and Non

Differential cCREs (FDR<0.1) between pre-T2D and Non

Differential cCREs (FDR<0.1) between T2D and pre-T2D

Differential cCREs (FDR<0.1) in terms of age

Differential cCREs (FDR<0.1) in terms of BMI

Differential cCREs (FDR<0.1) between male and female

Validation of beta cell differential cCREs using independent snATAC-seq dataset (S Figure 3)

Differential cCREs from Down-sampling analysis

Beta cell

Alpha cell

Delta cell

Beta cell subtype identification (Figure 2 and S Figure5)

Hypothesis test (S Figure 5d-e)

Identification of beta cell subtypes (Figure 2 b-d)

Beta subtype composition (Sex, BMI, Islet index, Age), S Figure 6a-d

Validation of beta cell subtype using independent snATAC-seq data (S Figure 6e-f)

Validation of beta cell subtype using independent computational method (S Figure 6h, k, l)

Alpha cell subtype identification (S Figure5 f, g)

Delta cell subtype identification (S Figure 5h, i)

Differential cCREs and genes between beta cell subtypes

Differential cCREs between beta cell subtypes (Figure 3b)

Correlation between ATAC and RNA (S Figure 7)

Differential genes between beta cell subtypes (Figure 3b)

Representative differential genes (Figure 3c)

Functional difference between beta cell subtypes (Patch-seq)

Classify patch-seq beta cell as beta_1 vs beta_2 (S Figure 8)

Different glucose concentrations (Figure S8c-d)

beta_1 vs beta_2 (Figure 3e-g)

Beta subtype (ND vs T2D), Figure 5a-b

Infer beta cell gene regulatory network (GRN) from multiome data

Infer TF binding sites

Infer potential TF-target regualtions with physical interactions

Identify TF-target with gene expression correlation

Identify TF-gene modules

Differential TF-gene modules between beta subtyeps (gene expression)

Differential TF-gene moduels (gene expression and motif enrichment)

TF-gene module heatmap

Regulations between TFs

cCREs activity and expression level of TFs

Correlations between TFs

Differential peaks during T2D progression (S Figure 10a-b)

beta-1

beta-2

Heatmap for differential cCREs during T2D progression

beta-1

beta-2

Beta cell subtype differential TF-gene modules during T2D progression (Figure 5c-d, S Figure 10 c-d)

Differential TF-gene modules during T2D progression

beta1

beta-2

Correlation between TFs